Potassium Carbonate → 4-((3-((4-(piperidin-1-yl)-2-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)phenyl)carbamoyl)benzyl)thio)benzoic acid

HRID 2409870Notes

Reaction equation

HRID 2409870 reaction equation
Cl[CH2:2][C:3]1[CH:4]=[C:5]([CH:39]=[CH:40][CH:41]=1)[C:6]([NH:8][C:9]1[CH:32]=[CH:31][C:30]([N:33]2[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]2)=[CH:29][C:10]=1[C:11]([NH:13][C:14]1[CH:18]=[CH:17][N:16]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=2)[N:15]=1)=[O:12])=[O:7].[SH:42][C:43]1[CH:51]=[CH:50][C:46]([C:47]([OH:49])=[O:48])=[CH:45][CH:44]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[N:33]1([C:30]2[CH:31]=[CH:32][C:9]([NH:8][C:6]([C:5]3[CH:4]=[C:3]([CH:41]=[CH:40][CH:39]=3)[CH2:2][S:42][C:43]3[CH:51]=[CH:50][C:46]([C:47]([OH:49])=[O:48])=[CH:45][CH:44]=3)=[O:7])=[C:10]([C:11](=[O:12])[NH:13][C:14]3[CH:18]=[CH:17][N:16]([C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:27])([F:28])[F:26])[CH:20]=4)[N:15]=3)[CH:29]=2)[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 957384-Mercaptobenzoic acidHCID 665882652-(3-(chloromethyl)benzamido)-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide

Product 1

HCID 566443444-((3-((4-(piperidin-1-yl)-2-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)phenyl)carbamoyl)benzyl)thio)benzoic acidYield 83.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a round bottom flask was placed a solution of intermediate 21a (0.0580 mmol, 1 equiv), 4-mercaptobenzoic acid (11 mg, 0.0696 mmol, 1.2 equiv), potassium carbonate (24 mg, 3 equiv), and DMF (1 mL). The solution was stirred at room temperature overnight. The solvent was evaporated at reduced pressure and the residue was partitioned between dichloromethane and water. The organic phase was dried (Na2SO4). The solvent was evaporated and the residue was purified by reverse phase HPLC eluting with 0.05% TFA in a water/acetonitrile gradient to give 34 mg of product. 1H-NMR (400 MHz, DMSO, ppm): δ 11.55 (s, 1H), 11.48 (s, 1H), 8.67 (d, J=2.6 Hz, 1H), 8.32 (d, J=8.3 Hz, 1H), 8.19 (S, 1H), 8.16 (d, J=7.8 Hz, 1H), 8.01 (s, 1H), 7.85-7.71 (m, 5H), 7.65 (d, J=7.5 Hz, 3H), 7.52 (t, J=7.7 Hz, 1H), 7.44 (d, J=8.7 Hz, 2H), 7.04 (d, J=2.7 Hz, 1H), 4.46 (s, 2H), 3.30 (s, 4H), 1.70 (s, 4H), 1.59 (s, 2H). MS (ES, m/z) 700 [M+H]+.

Workup

  1. customInto a round bottom flask was placed
  2. customThe solvent was evaporated at reduced pressure
  3. customthe residue was partitioned between dichloromethane and water
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. customThe solvent was evaporated
  6. customthe residue was purified by reverse phase HPLC
  7. washeluting with 0.05% TFA in a water/acetonitrile gradient

Sources & evidence

ORD record
ord-d20dc42574034cc0a47a887bc6dbc583
Source dataset
uspto-grants-2014_08
Patent number
US08815910B2

Reaction notes

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